Beyond Malaria: Causes of Non-Malarial Acute Undifferentiated Fever in Paediatric Out-Patient Clinics in Guinea Bissau

Background: With growing use of parasitological tests to detect malaria and decreasing incidence of the disease in Africa; it is necessary to increase our understanding of the causes of non-malarial illness, towards providing appropriate management. This research investigates causes of non-malarial undifferentiated acute fever in paediatric out-patients in Guinea Bissau. Methods: Children 0-5 years presenting acute fever (≥38o) or history of fever for less than 48 hours, negative rapid diagnostic test (RDT) and no signs of organ specific disease were recruited at the out-patient clinic of 3 facilities during 54 consecutive weeks (dry and rainy season). Medical history was recorded and blood, nasopharyngeal, stool and urine samples were collected and tested for the presence of 40 different potential aetiological causes of fever. Results: In total, 48.336 laboratory analyses were made on samples of 739 children presenting with acute fever of unknown origin and another 2.277 laboratory analysis on samples of 69 children enrolled as controls. The protocol was successful in determining a potential aetiological cause of acute fever in samples of 544 (73.61%) cases. The 544 individuals with positive samples, on average had 1.55 (sd=0.80) microorganisms identified, 333 (45.06%) had only one positive sample. Respiratory viruses were the most frequently identified pathogens, present in the nasopharynx samples of 435 (58.86%) cases, followed by bacteria detected in blood samples of 167 (22.60%) cases. Despite presenting negative RDT, P. falciparum was identified in samples of 24 (3.25%) patients and 1 (1.45%) control. Conclusions: This research provides a description of the aetiological causes of non-malarial acute fever in a West African context. Evidence of viral infections were more commonly found than bacteria or parasites. Funding: This study was entirely funded by Medecins Sans Frontieres, Barcelona-Athens Operational Centre, Insitut Pasteur Dakar and Institut Hospitalo-Universitaire Mediterranee. Declaration of Interest: Researches deny any potential conflict of interest. Ethical Approval: The protocol and its procedures were approved by two independent ethics committees (MSF's and Guinea Bissau's INASA) and are in accordance with the Declaration of Helsinki. All authors vouch for the accuracy and completeness of the data and the fidelity of the study to the protocol.